The present invention relates to a magnetic field resonance imaging apparatus, and more particularly to a magnetic field resonance imaging apparatus suitable for high-speed imaging with high resolution.
With the decrease in candidate compounds for new medicines and the increase in attention to security for the human body, the cost of new drug development by pharmaceutical companies is dramatically increasing and accordingly the number of mice used for animal experiment is also remarkably increasing. The demand for decreasing the number of small animals used for experiment in the stage of animal experiment called pre-clinic is increasing from the viewpoint of cost reduction and small animal protection. Furthermore, there is an increasing demand for a diagnostic imaging tool which allows observation and experiment with the living body as a support tool for medications development which makes it possible to observe drug effect in the living body and examine effect of a drug designed by a specific part-targeting of the living body.
In connection with conventional technologies concerning the above, such as MRI (nuclear magnetic resonance imaging) using nuclear magnetic resonance (NMR) and ESR-CT (electron spin resonance imaging) using electron spin resonance (ESR), commercial apparatuses targeting small animals have already been put on the market. CW (continuous wave)-based ESR-CT is used in many cases while pulse-based ESR-CT is studied in rare cases. With a magnetic resonance imaging system aiming at imaging in the living body, the frequency is limited to a radio frequency of 1.2 GHz or lower to image a deep portion of the living body even in case of a small animal, because of attenuated irradiation electromagnetic wave caused by water in the living body.
Irrespective of MRI or ESR-CT, with magnetic resonance CT, a gradient coil system for specifying a location where a signal is generated is placed in a uniform static magnetic field. Then a gradient field strength is varied for imaging. In this case, magnetic resonance CT is characterized in that the origin of coordinates of a shot image agrees with the origin of coordinates of the gradient coil system. In the case of MRI, since the hydrogen atomic nucleus (proton) is subjected to imaging, morphological images of the living body are obtained. Therefore, there has been a problem of finding out a target image from a huge amount of morphological images in order to discover an affected region. In the case of ESR-CT, since a radical contrast agent specific to ESR is applied to a small animal to image a distribution, it is difficult to obtain morphological images. However, since the contrast agent distribution is immediately imaged, ESR-CT is characterized in that finding out an affected region is easy if it is linked with the contrast agent distribution.
Hereinafter, the present invention is applied to ESR-CT technology using electron spin resonance (ESR) and therefore will be disclosed taking ESR-CT into consideration.
ESR-CT comprises a static magnetic field generator for generating a uniform magnetic space as a space for measuring a small animal (a measured space); a gradient coil system for imaging; an RF probe for radio wave transmission and reception; and a console system for controlling these elements. In the case of the CW method, a field scanning coil system is additionally provided. In the actual CW method, a field modulation coil system is additionally provided to apply AC field modulation for superposition on field scanning. However, the field modulation coil system is not related to the present invention and therefore will be omitted in the following disclosure.
When performing diagnostic imaging of the living body of an experimental small animal under anesthesia to alleviate the burden to the living body, the imaging time is limited to about 15 minutes because of the physical strength of the small animal. In the case of imaging under weak anesthesia or without anesthesia, it is desirable to complete imaging within a shorter period of time because there is a risk that the animal wriggles the body. When observing the living body of a small animal with time, it is valuable to make the imaging time as short as possible. The reduction in the imaging time is a pressing issue also from the viewpoint of efficient diagnostic imaging. With conventional MRI or ESR-CT, there has not been much demand for performing diagnostic imaging of the living body of an experimental small animal, and therefore the problem of the long imaging time has not been emerged as a common problem.
As a “molecule imaging” tool which visualizes biological reaction in the living body by imaging, on the other hand, the clearness of image, i.e., high spatial resolution is required. Although it is best to image the living body with high speed and high resolution, actual needs do not necessarily require high speed and high resolution. For example, there are two different objects of visualization of biological reaction. One is to survey the whole living body of a small animal, etc., and the other is to observe minutely a target portion. It is desirable that both objects of imaging be accomplished with an identical single apparatus. When surveying the whole living body, high-speed imaging is required even if the spatial resolution is given up to some extent. When observing minutely a target portion, there are two different cases. One is observing a predetermined target portion (for example, when a known lesion in the kidney is observed or when the function of the kidney is observed), and the other is observing a lesion discovered from images shot by surveying the whole living body (by means of a kind of an optical microscope or zoom-in function of a digital camera).
Conventional ESR-CT apparatuses using an electromagnet as a static magnetic field generator have the following three drawbacks for the above-mentioned demands, disturbing realization of the object of the present invention, i.e., high-speed imaging and high spatial resolution.
(1) High-speed switching of gradient field cannot be performed.
(2) High-speed field scanning cannot be performed.
(3) It is difficult to image an intentionally targeted region (desired portion) with a high spatial resolution of 1 mm or less.
The reason for (1), “High-speed switching of gradient field cannot be performed” will be explained below.
The gap between the pole pieces for forming a measured space (a region subjected to imaging, such as a mouse) is small. Therefore, when installing a gradient coil system, gradient field coils will be arranged next to the yokes immediately near the pole pieces. As a result, high-speed switching of gradient field generates an eddy current in the yokes, resulting in distortions and artifacts in the image. Therefore, high-speed switching cannot actually be realized. The eddy current generated in the yokes increases with decreasing distance between the gradient field coils and the yokes and increasing switching speed of the gradient field.
In the case of ESR, relaxation time T1 which determines an upper limit of high-speed switching of gradient field strength is as short as 10 μs at maximum, and therefore it is expected that the imaging speed be increased taking advantage of this short relaxation time. Although it is desirable to set an ultrashort switching time of gradient field strength to 30 to 50 μs (equivalent to a frequency of 20 to 33.3 kHz), it has not been realized for the above-mentioned reason.
The reason for (2), “High-speed field scanning cannot be performed” will be explained below.
(i) With conventional commercial ESR-CT, a leak magnetic field is confined in the yokes to reduce a magnetic field leak line (5-G line), and an electromagnet structure with yokes is employed to improve the current magnetic field efficiency. When the magnetic field is confined in the yokes, the flux density per unit sectional area of a magnetic circuit increases, preventing time change of a coil current and disturbing high-speed field scanning. This is attributable to an increase in the effective inductance of a coil. As a result, it has taken a very long time for imaging.(ii) If the gap between the pole pieces for forming a measured space (a region subjected to imaging, such as a mouse) is further increased, there is no other choice to enlarge the area of opposed surfaces of the pole pieces in order to guarantee the magnetic field homogeneity. With the electromagnet with yokes, therefore, the coil diameter is increased resulting in a larger yoke structure. Then, the effective inductance of the coil increases, making it further difficult to perform high-speed field scanning and resulting in an increased weight.
For above-mentioned (1) and (2), a study on an air-core electromagnet without yokes has been started with a view to improvement of commercial ESR-CT with an electromagnet with yokes (G. A. Rinard, et al.: Magnetic Resonance Engineering, Vol. 15, pages 51-58, 2002). In this example, the resonance magnetic field homogeneity of a measured space (a region subjected to imaging, such as a mouse) is achieved by an air-core coil having a resonance magnetic field strength of 90 G (equivalent to a frequency of 250 MHz), and therefore the following problems arise:
(A) The use of a coil having a large diameter (for example, 800 mm) is necessary. Since it is necessary to draw a large current (10 to 20 A), the stability of the magnetic field cannot be ensured by commercial power supply.
(B) Since inductance L increases because of the enlarged coil diameter, a time constant increases close to about 100 ms (equivalent to a frequency of about 10 Hz) prolonging the time of static field scanning, although not so long as that for an electromagnet with yokes.(C) The gross weight of the coil system including the large-diameter coil and the gradient field coils as well as the power supply system increases.(D) The magnetic field leak line (5-G line) increases in length to 2 m, remarkably limiting the operability and installation space. In consideration of influences on electronic devices and the human body, a structure which can make the leak magnetic field line (5-G line) compact is required for commercial systems.
If the resonance magnetic field increases to about 90 G to 400 G, the coil diameter and the coil current further increase and therefore the above-mentioned problems will become more noticeable.
If the coil current is made constant, the area of the space having a uniform resonance magnetic field of a measured space (a region subjected to imaging, such as a mouse) is uniquely determined by the coil diameter. Therefore, when the resonance magnetic field is increased, there is no other choice to enlarge the coil diameter in order to ensure the same area of the space having a uniform resonance magnetic field. In this case, the time of field scanning becomes longer, the system heavier, and the magnetic field leak line (5-G line) longer.
Therefore, the present air-core coil electromagnet system is useful for demonstration but not suitable for commercial ESR-CT apparatuses.
The reason for (3), “It is difficult to image an intentionally targeted (desired portion) region with a high spatial resolution of 1 mm or less” will be explained below.
With a conventional ESR-CT apparatus, the gradient coil system and the RF probe system are fixed with respect to a region having a uniform static magnetic field. Therefore, moving operations are only translation and rotation of the subject (imaging target, such as a mouse). Only a region near a center determined by the gradient coil system can be observed with high resolution. A desired portion cannot necessarily be imaged with high resolution. To image other regions with high resolution, it was necessary to perform translation and rotation of the subject, and then arrange a desired portion near a center determined by the gradient coil system.
To be in more detail, with the conventional ESR-CT apparatus, an absorption width ΔH of the radical under measurement is as large as about 1 to 2 G (Gauss). Therefore, in order to realize a spatial resolution of 1 mm or less in terms of the ratio of an absorption width ΔH (theoretical spatial resolution) to a gradient field strength G (gradient field strength), ΔH/G, it is necessary to set the gradient field strength to 10 to 20 G/cm or more. As a result, the power to be supplied to the gradient coil system became too high, and accordingly measurement was limited by a spatial resolution of about 1 mm because of heat generation by the gradient coil system.
On the other hand, a spatial area of about 35 mm is required as a measured space (region under measurement of a small animal, such as a mouse). Therefore, in the case of a typical resonance frequency of 250 MHz (equivalent to a resonance magnetic field strength H0 of 90 G) of the ESR-CT apparatus, 35 mm×10 G/cm=35 G results when the gradient field strength is 10 G/cm. Therefore, the magnetic field strength at both ends of the measured space is 72.5 G (=90−17.5) and 107.5 G (=90+17.5) respectively, resulting in a deviation of as large as ±19.4% from the resonance magnetic field. Under this condition, imaging of the entire measured space is difficult.
In this example, it was possible to perform imaging with a spatial resolution of 1 mm or less only in a small region, H0/(G×Q) (=90 G/(10 G/cm×80)=1.125 mm), at the center of the measured space. Here, Q denotes a Q value of an RF probe, which is about 80 when a small animal is inserted.
Therefore, when imaging a large region, there is no other choice to reduce the gradient field strength to give up the spatial resolution and therefore high-resolution imaging of the entire measured space was difficult.
Furthermore, imaging can be performed through translational movement of the center of the measured space in the Z direction (a direction of the static magnetic field) by changing the current of the electromagnet. However, since translational movement in the X and Y directions is not possible, it was not possible to observe a desired portion in the measured space with high resolution.
Since a conventional ESR-CT apparatus is based on the CW method (continuous wave method) which does not practically require a limitation on the absorption width of the radical under measurement, it is necessary to make the static field strength variable in a wide range, and a permanent magnet which fixes the magnetic field is not applied except for a micro system, such as a portable ESR with high frequency in the GHz range (for example, Japanese Patent No. 2640377). Such a permanent magnet type portable ESR has been using a pair of opposed permanent magnets as a static field generator like open MRI (for example, Japanese Patent Application Laid-Open No. 9-299351). In this case, it is usual to arrange a permanent magnet having the almost same junction area as opposed area of the pair of pole pieces.
MRI using a permanent magnet, which is also referred to as open MRI, makes it possible to secure a wide open space unlike a cylindrical superconducting magnet. MRI has been said to be a human-friendly system. However, even in the case of an open MRI system, the distance between the pole pieces is short because the ratio of the human size LM along the direction of the pole pieces to the distance La between the pole pieces, LM/La, is around 0.8. Also in the case of a compact MRI system using a permanent magnet, the distance between the pole pieces is still short because the ratio of the dimensions of the subject to the distance between the pole pieces is around 0.7 to 0.9. The primary cause of the short distance between the pole pieces is that there was no other choice to place top priority on raising the magnetic resonance sensitivity by maximizing resonance magnetic field strength.